David Lu (davidlu@gmail.com)

Graduate Program:  Molecular Pathology
Lab PI: Paul A. Insel, M.D.
Undergraduate Institution: University of California, Berkeley
Med-into-Grad clinical training area: Cardiovascular Disease
Main clinical mentors:
Dr. Kirk Knowlton  kknowlton@ucsd.edu
 Dr. Sotirios Tsimikas stsimikas@AD.UCSD.EDU
 

Quote: “I feel the greatest benefit of my clinical experience is the opportunity to improve my knowledge of the large-scale physiological context for the various molecular and pharmacological studies I conduct in research lab. By augmenting my knowledge, I feel better equipped to identify more relevant disease states and model systems in which to perform my research on the cellular level.”

Rational for Med-into-Grad training:
My research focuses on the signaling mechanisms that induce and reverse cardiac fibrosis and hypertrophy. Particularly I focus on the role of the cardiac fibroblast in mediating heart remodeling in disease conditions such as myocardial infarction (MI), pressure-overload induced hypertrophy, and heart failure. My work in lab includes in vitro studies that would ideally integrate into in vivo animal models of heart disease. Not only does the Med-into-Grad program provide me with an incredibly relevant environment in which to observe, in patients, the ramifications of the cardiovascular diseases we study, it also familiarizes me with the many tools to assess disease progression. Because in lab, we inevitably spend much of our time focused on the reductionist approach in studying cell function and signaling using classic in vitro pharmacology methods, being able to learn about the heart as an organ and its interactions with the human body as a whole was very useful in both an education and research standpoint.

Medical training and identification of medically-relevant research issues:  Shadowing a fellow through clinic was very interesting since it gave me a first hand look at the potential severity of the various cardiac diseases. Meeting a woman with severe aortic stenosis or seeing patients in the CCU with acute heart failure were all experiences that highlighted the prevalence and severity of many of these diseases and how important is it is to continue research in this area. What I enjoyed most in my experience was observing procedures done in the cardiac catheterization lab and in the echocardiogram clinic. It was with these procedures I could observe the manifestations of disease directly on the heart. Even though echo is a fairly simple procedure, being able to visualize the left ventricle (LV) hypertrophy of a patient with aortic stenosis or LV dilation of an elderly man with early stage heart failure was both interesting and informative. It was through this I gained a much better understanding of both the anatomy and physiology of the heart. I feel the greatest benefit of my clinical experience is the opportunity to improve my knowledge of the large-scale physiological context for the various molecular and pharmacological studies I conduct in research lab. By augmenting my knowledge, I feel better equipped to identify more relevant disease states and model systems in which to perform my research on the cellular level. As a Ph.D. graduate student, the downstream applications of many of the disease-related research we do are not always lucid and evident. However, having a more solid medical understanding provides me with groundwork in which to focus the most relevant aspects of my research.

Potential Research collaborations: As mentioned in my research proposal, I am interested in the contribution of cardiac fibroblasts in the progression of aortic stenosis and calcification. Recent studies have suggested the important role of fibroblast activation in inducing extracellular matrix protein production that could lead to valvular and aortic calcification. In addition, the constant major focus of my research is on the mechanisms of cardiac remodeling in response to injury and heart failure. Dr. Barry Greenburg is a clinician and P.I. who is an expert in the field of heart remodeling. Through the course of the Med-into-Grad program, I was able to introduce myself to him. In the future I would potentially like to continue a dialogue with him and members of his lab. He has conducted interesting research related to crosstalk between cardiac fibroblasts and myocytes and this topic is very relevant to studies of my own. We have drafted a few initial ideas in our lab that we would like to pursue, and I feel that Dr. Greenburg’s expertise may be an excellent resource to have.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs: I feel that I have received an excellent view of the various diagnostics and interventional therapeutics commonly used in cardiovascular disease. Between the various techniques in echocardiograms, angiograms and electrocardiograms, cardiologists have an incredibly useful and informative array of diagnostic tools at their disposal. They are able to track detailed dimensions, blood flow, pressures and motion of the heart, image the various coronary arteries supplying blood to the myocardium, and monitor the electrical signaling and pacing of the heart. I would be hard-pressed to be able to devise a new and improved diagnostic technique. My goal during this experience was to familiarize myself with the state-of-the-art available techniques for such physiological measurements. In the case of potential therapeutics, since my research involves elucidating the signaling pathways mediating fibrosis in response to pathological remodeling, future clinical applicability is a distinct possibility. We are focusing on G-protein coupled receptor mediated pathways: ß-adrenergic receptors and purinergic receptors, and also on angiotensin receptors, which are all very relevant in the heart. These are common therapeutic targets in the cardiovascular setting. While my research will most likely not result in the immediate identification of a novel therapeutic, better understanding of cellular regulation will lay the groundwork for refining current therapeutics as well as understanding mechanisms of disease pathogenesis.

Diagnostic & Therapeutic collaborations:  As previously mentioned, I have met doctors who’s research is very much related to my own, most notably Dr. Barry Greenburg. However, possible collaborations between myself and the people I have met in the clinical setting will be based primarily on hypothesis-driven research centering on signaling mechanisms. As such, the possibility of novel diagnostic and therapeutic will mostly likely not arise immediately from the results of my research. However, that does not preclude the possibility of future research based on our current studies evaluating the use of new therapeutics or diagnostics. I do not feel that this is any way a drawback or fault of the Med-into-Grad program. On the contrary, even though my goal is not to directly find new drugs for clinicians to use, the program was an enormous benefit to my own personal education and my understanding of the system in which we study.

Long term impact: The Med-into-Grad program has given me a better understanding of the physiological system I study, especially in the context of the end goal of biomedical research: helping the patient. It has reaffirmed my belief that what I do in lab does have future applicability in a medical setting, which is an important consideration in the research that I would like to conduct. It has boosted my enthusiasm for my research since I now I have seen first hand the deleterious effect that various forms of cardiovascular disease has on the patient. Interacting with other medical doctors, particularly ones that also run research labs has given me additional skills in setting up potential collaborations and has helped established a growing network of contacts that I would like to explore during my residence as a graduate student.

Student-specific experiences:  All of the doctors and fellows that I have had the pleasure of shadowing and interacting with have been enormously helpful and very approachable. It has made for a great experience from a personal and educational standpoint.

Advice for new trainees--Autumn preparatory quarter:  Personally, I very much enjoyed the Cardiovascular Science Conference Series that meets every Friday morning in CMG. It is a basic science seminar series that focuses mainly on the various facets of cardiovascular research. Many of the speakers touch on topics that are very relevant to my own research. Though it does not prepare you as much for the clinical setting as other events such as Interventional Cardiology Conference of Cath Conference, I feel that the “take-home messages” from the Cardiovascular Science Conference Series have the most practical applicability to my work. I will definitely continue to attend this series for as long as I am in graduate school. In addition being familiar with the physiology of the heart is essential for a fruitful clinical experience. It is important to know the general anatomy of the heart, how it functions, the physiological ramifications of disease on the system, and the basic treatments for such diseases. In the clinic, doctors will be using vocabulary and drug names that will be foreign to a typical graduate student unless he/she has spent some time perusing the basics of cardiology from either the Braunwald textbook or the pathology text.

Advice for new trainees—Winter clinical training quarter:  As everyone else has no doubt mentioned: ask questions! The doctors, fellows and residents are usually exceedingly interested in teaching. Most of them are very approachable but all of them are also very busy. As such, they will spend very little time asking if you have any questions. However that does not mean that they do not enjoy teaching a graduate student. Dr. Tsimikas especially is very fond of teaching. As long as you are engaging yourself in the environment, don’t hesitate to ask questions or ask for clarification. I feel that this is important as well since it shows the doctors that you yourself are interested in what they may be showing you. Also, when attending seminars or conferences for the first time, try not to be shy. The Cath Conference for example consists of only 8-10 people, all of who are doctors. That can be intimidating at first, but try to introduce yourself to as many people as possible. The residents and fellows especially can all remember what it was like to be a student, and are usually pretty approachable. In clinic, dress appropriately. A tie usually isn’t necessary, but be sure to wear a dress shirt and slacks. You will be interacting directly with patients. Most patients have no problem talking to you about their ailments, but it is a very professional environment so be sure to dress appropriately.

Take home perspective on Med-into-Grad at UCSD: I very much enjoyed the Med-into-Grad program at UCSD and would highly recommend it to any future students that have an interest in seeing the clinical manifestations in any disease they study. Not only does it give you a better medical grounding for your research, it allows for developing possible collaborations with other faculty members. It also heightened my enthusiasm for my research since the disease in my mind is no longer a description of symptoms read off the background sections from various journal articles. Being able to see patients first hand and the related diagnostics and therapeutics have made this possible.